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Emergence of multiclass drug-resistance in HIV-2 in antiretroviral-treated individuals in Senegal: implications for HIV-2 treatment in resouce-limited West Africa.

ABSTRACT: The efficacy of various antiretroviral (ARV) therapy regimens for human immunodeficiency virus type 2 (HIV-2) infection remains unclear. HIV-2 is intrinsically resistant to the nonnucleoside reverse-transcriptase inhibitors and to enfuvirtide and may also be less susceptible than HIV-1 to some protease inhibitors (PIs). However, the mutations in HIV-2 that confer ARV resistance are not well characterized.Twenty-three patients were studied as part of an ongoing prospective longitudinal cohort study of ARV therapy for HIV-2 infection in Senegal. Patients were treated with nucleoside reverse-transcriptase inhibitor (NRTI)- and PI (indinavir)-based regimens. HIV-2 pol genes from these patients were genotyped, and the mutations predictive of resistance in HIV-2 were assessed. Correlates of ARV resistance were analyzed.Multiclass drug-resistance mutations (NRTI and PI) were detected in strains in 30% of patients; 52% had evidence of resistance to at least 1 ARV class. The reverse-transcriptase mutations M184V and K65R, which confer high-level resistance to lamivudine and emtricitabine in HIV-2, were found in strains from 43% and 9% of patients, respectively. The Q151M mutation, which confers multinucleoside resistance in HIV-2, emerged in strains from 9% of patients. HIV-1-associated thymidine analogue mutations (M41L, D67N, K70R, L210W, and T215Y/F) were not observed, with the exception of K70R, which was present together with K65R and Q151M in a strain from 1 patient. Eight patients had HIV-2 with PI mutations associated with indinavir resistance, including K7R, I54M, V62A, I82F, L90M, L99F; 4 patients had strains with multiple PI resistance-associated mutations. The duration of ARV therapy was positively associated with the development of drug resistance (P = .02). Nine (82%) of 11 patients with HIV-2 with no [corrected] detectable ARV resistance had undetectable plasma HIV-2 RNA loads (<1.4 log(10) copies/mL), compared with 3 (25%) of 12 patients with HIV-2 with detectable ARV resistance (P = .009). Patients with ARV-resistant virus had higher plasma HIV-2 RNA loads, compared with those with non-ARV-resistant virus (median, 1.7 log(10) copies/mL [range, <1.4 to 2.6 log(10) copies/mL] vs. <1.4 log(10) copies/mL [range, <1.4 to 1.6 log(10) copies/mL]; P = .003).HIV-2-infected individuals treated with ARV therapy in Senegal commonly have HIV-2 mutations consistent with multiclass drug resistance. Additional clinical studies are required to improve the efficacy of primary and salvage treatment regimens for treating HIV-2 infection.

SUBMITTER: Gottlieb GS

PROVIDER: S-EPMC3671065 | biostudies-literature | 2009 Feb

REPOSITORIES: biostudies-literature

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Emergence of multiclass drug-resistance in HIV-2 in antiretroviral-treated individuals in Senegal: implications for HIV-2 treatment in resouce-limited West Africa.

Gottlieb Geoffrey S GS Badiane Ndeye Mery Dia NM Hawes Stephen E SE Fortes Louise L Toure Macoumba M Ndour Cheikh T CT Starling Alison K AK Traore Fatou F Sall Fatima F Wong Kim G KG Cherne Stephen L SL Anderson Donovan J DJ Dye Stefanie A SA Smith Robert A RA Mullins James I JI Kiviat Nancy B NB Sow Papa Salif PS

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America 20090201 4

<h4>Background</h4>The efficacy of various antiretroviral (ARV) therapy regimens for human immunodeficiency virus type 2 (HIV-2) infection remains unclear. HIV-2 is intrinsically resistant to the nonnucleoside reverse-transcriptase inhibitors and to enfuvirtide and may also be less susceptible than HIV-1 to some protease inhibitors (PIs). However, the mutations in HIV-2 that confer ARV resistance are not well characterized.<h4>Methods</h4>Twenty-three patients were studied as part of an ongoing ...[more]

PMID: 19143530

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Project description:BackgroundEpidemic HIV-2 (groups A and B) emerged in humans circa 1930-40. Its closest ancestors are SIVsmm infecting sooty mangabeys from southwestern Côte d'Ivoire. The earliest large-scale serological surveys of HIV-2 in West Africa (1985-91) show a patchy spread. Côte d'Ivoire and Guinea-Bissau had the highest prevalence rates by then, and phylogeographical analysis suggests they were the earliest epicenters. Wars and parenteral transmission have been hypothesized to have promoted HIV-2 spread. Male circumcision (MC) is known to correlate negatively with HIV-1 prevalence in Africa, but studies examining this issue for HIV-2 are lacking.MethodsWe reviewed published HIV-2 serosurveys for 30 cities of all West African countries and obtained credible estimates of real prevalence through Bayesian estimation. We estimated past MC rates of 218 West African ethnic groups, based on ethnographic literature and fieldwork. We collected demographic tables specifying the ethnic partition in cities. Uncertainty was incorporated by defining plausible ranges of parameters (e.g. timing of introduction, proportion circumcised). We generated 1,000 sets of past MC rates per city using Latin Hypercube Sampling with different parameter combinations, and explored the correlation between HIV-2 prevalence and estimated MC rate (both logit-transformed) in the 1,000 replicates.Results and conclusionsOur survey reveals that, in the early 20th century, MC was far less common and geographically more variable than nowadays. HIV-2 prevalence in 1985-91 and MC rates in 1950 were negatively correlated (Spearman rho = -0.546, IQR: -0.553--0.546, p≤0.0021). Guinea-Bissau and Côte d'Ivoire cities had markedly lower MC rates. In addition, MC was uncommon in rural southwestern Côte d'Ivoire in 1930.The differential HIV-2 spread in West Africa correlates with different historical MC rates. We suggest HIV-2 only formed early substantial foci in cities with substantial uncircumcised populations. Lack of MC in rural areas exposed to bushmeat may have had a role in successful HIV-2 emergence.

Project description:BACKGROUND:Species of the Tabanidae are potent vectors of human and animal diseases, but they have not been thoroughly investigated to date. In Senegal (West Africa), little information is available on these dipterans. Our objective in this study was to investigate Senegalese tabanids and their diversity by using molecular and proteomics approaches, as well as their associated pathogens. METHODS:A total of 171 female tabanids were collected, including 143 from Casamance and 28 from Niokolo-Koba. The samples were identified morphologically by PCR sequencing and by MALDI-TOF MS, and PCR analysis was employed for pathogen detection and blood-meal characterization. RESULTS:The morphological identification revealed four species concordantly with the molecular identification: Atylotus fuscipes (79.5%), Tabanus guineensis (16.4%), Chrysops distinctipennis (3.5%) and Tabanus taeniola (0.6%) (not identified by PCR). The molecular investigation of pathogens revealed the presence of Trypanosoma theileri (6.6%), Leishmania donovani (6.6%), Setaria digitata (1.5%), Rickettsia spp. (5.1%) and Anaplasmataceae bacteria (0.7%) in A. fuscipes. Tabanus guineensis was positive for L. donovani (35.7%), S. digitata (3.6%) and Anaplasmataceae (17.8%). Leishmania donovani has been detected in 50% of C. distinctipennis specimens and the only T. taeniola specimen. No Piroplasmida, Mansonella spp. or Coxeilla burnetii DNA was detected. In addition to humans (96.43%), Chlorocebus sabeus, a non-human primate, has been identified as a host of (3.57%) analysed tabanids. MALDI-TOF MS enabled us to correctly identify all tabanid species that had good quality spectra and to create a database for future identification. CONCLUSIONS:Tabanids in Senegal could be vectors of several pathogens threatening animal and public health. To fully characterize these dipterans, it is therefore necessary that researchers in entomology and infectiology employ molecular characterization and mass spectrometric techniques such as MALDI-TOF MS to analyse these dipterans in Senegal and West Africa.

Project description:To assess the virological response, genotypic resistance profiles, and antiretroviral plasma concentrations in HIV-2 antiretroviral-treated (antiretroviral therapy, ART) patients in Côte d'Ivoire.A cross-sectional survey was conducted among HIV-2 patients receiving ART. Plasma HIV-2 viral load was performed using the Agence Nationale de Recherche sur le SIDA et les hépatites virales (ANRS) assay. Protease and reverse transcriptase sequencing was performed using in-house methods and antiretroviral plasma concentrations were assessed using ultra performance liquid chromatography combined with tandem mass spectrometry.One hundred and forty-five HIV-2-treated patients were enrolled with a median CD4 cell count of 360 cells/?l (interquartile range, IQR?=?215-528). Median duration of ART was 4 years (IQR?=?2-7) and 74% of patients displayed viral load less than 50?copies/ml. Median plasma HIV-2 RNA among patients with viral load more than 50?copies/ml was 3016?copies/ml (IQR?=?436-5156). Most patients (84%) received a lopinavir/ritonavir-based regimen. HIV-2 resistance mutations to nucleoside reverse transcriptase inhibitors and protease inhibitors were detected in 21 of 25 (84%) and 20 of 29 (69%) samples, respectively. The most prevalent nucleoside reverse transcriptase inhibitor resistance mutations were M184I/V (90%), Q151M (24%), and S215F/Y (24%). The most prevalent protease inhibitor resistance mutations were V47A (60%) and I54M (30%). Median CD4 cell counts were 434 cells/?l (292-573) and 204 cells/?l (122-281) in patients with viral load less than 50?copies/ml and those exhibiting virological failure (P?<?0.0001), respectively. The proportions of patients with adequate antiretroviral plasma concentrations were 81 and 93% in patients displaying virological failure and in those with viral load less than 50?copies/ml, respectively (P?=?0.046), suggesting good treatment adherence.We observed adequate drug plasma concentrations and virological suppression in a high proportion of HIV-2-infected patients. However, in cases of virological failure, the limited HIV-2 therapeutic arsenal and cross-resistance dramatically reduced treatment options.

Project description:BackgroundNon-communicable diseases, including hypertension (HTN), are increasingly recognized as important causes of morbidity and mortality among people living with HIV (PLHIV) in resource-limited settings. The goals of this study were to determine the prevalence of HTN among PLHIV in Senegal over time and to identify predictors of HTN among HIV-positive versus HIV-negative adults.MethodsWe conducted a retrospective study using data from individuals enrolled in previous studies in Senegal from 1994-2015. Blood pressure (BP) measurements taken during study visits were used for analysis. HTN was defined as systolic BP?140 or diastolic BP?90. We used logistic regression to identify predictors of HTN.ResultsWe analyzed data from 2848 adults (1687 HIV-positive, 1161 HIV-negative). Among PLHIV, the prevalence of HTN increased from 11% during 1994-1999 to 22% during 2010-2015. Among HIV-negative individuals, the prevalence of HTN increased from 16% to 32%. Among both groups, the odds of HTN more than doubled from 1994-1999 to 2010-2015 (HIV-positive OR 2·4, 95% CI 1·1-5·0; HIV-negative OR 2·6, 95% CI 1·5-4·6). One quarter of all individuals with HTN had stage 2 HTN. The strongest risk factor for HTN was obesity (HIV-positive OR 3·2, 95% CI 1·7-5·8; p<0·01; HIV-negative OR 7·8, 95% CI 4·5-13·6; p<0·01). Male sex and age ?50 were also predictive of HTN among both groups. Among HIV-positive subjects, WHO stage 1 or 2 disease was predictive of HTN and among HIV-negative subjects, having no formal education was predictive.ConclusionOver the past 20 years, the prevalence of HTN has doubled among both HIV-positive and HIV-negative adults in Senegal. Our study indicates that there is an increasing need for the integration of chronic disease management into HIV programs in Senegal. Furthermore, our findings highlight the need for enhanced prevention, recognition, and management of non-communicable diseases, including hypertension and obesity, among both HIV-positive and HIV-negative individuals in Senegal.

Project description:BackgroundUnderstanding the impact of food insecurity on HIV outcomes is critical for the development and implementation of effective, evidence-based interventions to address food insecurity and improve the HIV care cascade. We conducted a prospective, longitudinal study to determine the impact of food insecurity on HIV outcomes in Senegal, West Africa.MethodsHIV-infected individuals presenting for care and initiation of ART through the Senegalese National AIDS program in Dakar and Ziguinchor were eligible for enrollment. Data were collected using interviews, clinical evaluations, laboratory analyses, and chart review at enrollment, month 6, and month 12. Logistic regression was used to determine the association between food insecurity and HIV outcomes.ResultsAmong the 207 participants in this study, 70% were female and the median age was 37 years. The majority (69%) were food insecure at enrollment, 29% were severely food insecure, and 38% were undernourished. Nearly a third (32%) had no formal education, 23% practiced agriculture, and 40% owned livestock. The median daily food expenditure per person was $0.58. The median round trip transportation time to clinic was 90 min (IQR 30-240). The median cost of transportation to clinic was $1.74. At month 12, 69% were food insecure, 23% were severely food insecure, and 14% were undernourished. At month 12, 43% had not disclosed their HIV status; food insecurity was associated with non-disclosure of HIV-status due to fear of stigmatization and feelings of shame. Severe food insecurity was a strong predictor of loss to follow-up (OR 3.13 [1.08-9.06]) and persistent severe food insecurity was associated with virologic failure (OR 5.14 [1.01-26.29]) and poor adherence to ART 8.00 [1.11-57.57]. Poor nutritional status was associated with poor immunologic recovery (OR 4.24 [1.56-11.47]), virologic failure (OR 3.39 [1.13-10.21]), and death (OR 3.35 [1.40-8.03]).ConclusionSeverity and duration of food insecurity are important factors in understanding the relationship between food insecurity and HIV outcomes. Our findings highlight the importance of nutritional status, socioeconomic opportunity, and self-stigmatization in the complex pathway between food insecurity and HIV outcomes. Interdisciplinary, multisectoral efforts are needed to develop and implement effective interventions to address food insecurity among people living with HIV.

Project description:BackgroundFood insecurity can contribute to poor adherence to both tuberculosis treatment and HIV antiretroviral therapy (ART). Interventions that target food insecurity have the potential to increase treatment adherence, improve clinical outcomes, and decrease mortality. The goals of this study were to compare the feasibility, acceptability, and potential impact of implementing two different forms of nutrition support for HIV-TB co-infected adults in the Casamance region of Senegal.MethodsWe conducted a randomized pilot implementation study among HIV-TB co-infected adults initiating treatment for TB (ClinicalTrials.gov Identifier: NCT03711721). Subjects received nutrition support in the form of a local food basket or Ready-to-Use Therapeutic Food (RUTF), distributed on a monthly basis for six months.ResultsA total of 178 monthly study encounters were completed by 26 HIV-TB co-infected adults; 14 received food baskets and 12 received RUTF. For both the food basket and RUTF, 100% of subjects obtained the supplement at every study encounter, transferred the supplement from the clinic to their household, and consumed the supplement. The food basket had greater acceptability and was more likely to be shared with members of the household. Adherence to TB treatment and ART exceeded 95%, and all outcomes, including CD4 cell count, hemoglobin, nutritional status, and food security, improved over the study period. All subjects completed TB treatment and were smear negative at treatment completion. The total cost of the local food basket was approximately $0.68 per day versus $0.99 for the RUTF.ConclusionThe implementation of nutrition support for HIV-TB co-infected adults in Senegal is feasible and may provide an effective strategy to improve adherence, treatment completion, and clinical outcomes for less than 1 USD per day. Further studies to determine the impact of nutrition support among a larger population of HIV-TB co-infected individuals are indicated.

Dataset Information

Emergence of multiclass drug-resistance in HIV-2 in antiretroviral-treated individuals in Senegal: implications for HIV-2 treatment in resouce-limited West Africa.

Publications

Emergence of multiclass drug-resistance in HIV-2 in antiretroviral-treated individuals in Senegal: implications for HIV-2 treatment in resouce-limited West Africa.

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